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Objectives: Current guidelines support the use of screening for early detection in breast, prostate, colorectal and cervical cancer. The purpose of this study was to evaluate whether insurance status predicts for more advanced disease in these four currently screened cancers. Study Design: The Surveillance, Epidemiology, and End Results (SEER) database was queried for breast, prostate, colorectal and cervix in patients aged 18e64 years. The database was queried from 2007 to 2011, with 425,614 patients with known insurance status included. Methods: Multinomial logistic regression was used to evaluate insurance status and cancer presentation. Results: Under multivariate analysis for breast cancer, uninsured patients more often had invasive disease (odds ratio [OR]: 1.55), T- (OR: 2.00), N- (OR: 1.59) stage, and metastatic disease (OR: 3.48), and were more often high-grade (OR: 1.21). For prostate cancer, uninsured patients again presented more commonly with higher T-stage (OR: 1.45), nodal (OR: 2.90) and metastatic (OR: 4.98) disease, in addition to higher prostate-specific antigen (OR: 2.85) and Gleason score (OR: 1.65). Colorectal cancer had similar findings with uninsured individuals presenting with more invasive disease (OR: 1.78), higher T (OR: 1.86), N (OR: 1.22), and M (OR: 1.58) stage, in addition to higher carcinoembryonic antigen levels (OR: 1.66). Similar results were seen for cervical cancer with uninsured having higher T (OR: 2.03), N (OR: 1.21), and M (OR: 1.45) stage. Conclusion: In the four cancers detected by screening exams, those without health insurance present with more advanced disease, with higher stage and grade, and more elevated tumour markers. [ABSTRACT FROM AUTHOR]

Purpose: To describe the histologic and volumetric changes in normal liver tissue after stereotactic body radiotherapy (SBRT) for liver metastases., Methods and Materials: Pre- and post-SBRT imaging studies were analyzed to evaluate the effect of SBRT on normal liver volume (NLV) in 15 patients treated in a prospective clinical trial. Two other patients underwent exploratory surgery after SBRT and histologic analyses of the irradiated liver were performed to characterize the pathologic effects of SBRT., Results: In the 15 patients studied quantitatively, the total NLV had decreased transiently at 2-3 months after SBRT and then began to regenerate at 3-8 months after SBRT. The median NLV reduction at the maximal observed effect was 315 cm(3) (range, 125-600) or 19% (range, 13-33%). Among the several dosimetric parameters evaluated, the strongest linear correlation was noted for the NLV percentage receiving 30 Gy as a predictor of maximal NLV reduction (r(2) = 0.72). The histologic changes observed 2 and 8 months after SBRT demonstrated distinct zones of tissue injury consistent with localized veno-occlusive disease., Conclusion: The well-demarcated focal parenchymal changes after liver SBRT (demonstrated both radiographically and histologically) within the high-dose zone are consistent with a threshold dose-induced set of phenomena. In contrast, the more global effect of NLV reduction, which is roughly proportional to whole organ dose parameters, resembles more closely an effect determined from radiobiologically parallel architecture. These observations suggest that modeling of normal tissue effects after liver SBRT might require different governing equations for different classes of effects.

Purpose: Red blood cell (RBC) transfusions or erythropoietin (EPO) can be used to evade the detrimental effects of anemia during radiotherapy, but the economic consequences of selecting either intervention are not well defined. The RBC transfusion needs during chemoradiotherapy for cervix cancer were quantified to allow comparison of RBC transfusion costs with the projected cost of EPO in this setting., Methods and Materials: For patients receiving pelvic radiotherapy, weekly cisplatin, and brachytherapy, the RBC units transfused during treatment were tallied. RBC transfusion costs per unit included the blood itself, laboratory fees, and expected value (risk multiplied by cost) of transfusion-related viral illness. EPO costs included the drug itself and supplemental RBC transfusions when hemoglobin was not adequately maintained. An EPO dosage based on reported usage in cervix cancer patients was applied., Results: Transfusions were given for hemoglobin <10 g/dL. Among 12 consecutive patients, 10 needed at least 1 U of RBC before or during treatment, most commonly after the fifth week. A total of 37 U was given during treatment, for an average of 3.1 U/patient. The sum total of the projected average transfusion-related costs was $990, compared with the total projected EPO-related costs of $3869., Conclusions: Because no proven clinical advantage has been documented for EPO compared with RBC transfusions to maintain hemoglobin during cervix cancer treatment, for most patients, transfusions are an appropriate and appealingly less expensive option.

Between 1989 and 1994, a prospective clinical trial tested the safety and efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy for patients with locally advanced cervix cancer. CBASF radiotherapy included 45 Gy/25 fractions to the pelvis and a 14.4 Gy/9 fraction concomitant boost to the primary tumor, followed by brachytherapy for a total point A dose of 85 Gy to 90 Gy. The 22 patients of International Federation of Gynecology and Obstetrics stages IIIA-IVA who received CBASF radiotherapy now have a median follow-up time of more than 8 years. The 7-year actuarial rates of local control and overall survival are 81% and 36%, respectively. Serious late toxicity included bowel injury requiring colostomy in eight patients within 2.5 years after treatment, but no other severe toxicity was observed after longer follow-up intervals. The local control and survival rates achieved with CBASF radiotherapy were higher than those observed within a matched contemporaneous cohort of patients treated with standard radiotherapy alone at the same institution (p = 0.1 for local control, 0.09 for survival). The encouraging trend toward improved tumor control, tempered by the complication rate, suggests an opportunity to apply more sophisticated radiotherapy techniques that might sustain the favorable effects of dose intensification while mitigating the normal tissue toxicity.

This patient with recurrent meningioma grossly involving the frontal bone underwent craniotomy and tumor resection. During the procedure a bone flap was irradiated extracorporeally at a very high dose (120 Gy) sufficient to sterilize residual tumor cells, and the bone was then successfully replaced orthotopically for reconstruction. The use of autologous irradiated bone in this setting offers advantages over cadaveric transplantation and prosthetic implants. Radiation might cause less disruption of the bone's architecture than other techniques of tumor cell eradication.

Three-dimensional conformal radiotherapy is quickly becoming a standard radiation oncology practice at many academic and community-based departments. Three-dimensional conformal radiotherapy allows clinicians to deliver safer and more accurate treatments to patients. It is also being used to increase tumor doses for situations in which traditional radiation techniques have been unsuccessful. Current and future clinical trials of dose-escalated three-dimensional conformal radiotherapy will examine its ultimate clinical effectiveness.

The authors evaluated the feasibility of using digital fluoroscopic images for device placement verification and dosimetric planning for gynecologic brachytherapy. Adequate images were obtained rapidly, and the limited pincushion distortion on digital fluoroscopic images produced negligible variations in brachytherapy dose calculations compared with those calculated with standard radiographs. Intraoperative digital fluoroscopy can facilitate both placement verification and dosimetric planning for gynecologic brachytherapy.

Aggressive surgical and radiotherapeutic management of a patient with desmoplastic malignant melanoma arising from the mucosa of the oral cavity has resulted in disease-free survival of more than 2(1/2) years after diagnosis. This case represents only the tenth reported instance of desmoplastic malignant melanoma arising from the oral cavity and only the third for which survival has exceeded 2 years. Details of the clinical, histopathologic, and therapeutic features of the case are provided to augment the paucity of literature available to clinicians managing this rare disease.

Purpose: To determine the block margin that minimizes normal tissue irradiation outside of the planning target volume (PTV) for body stereotactic radiotherapy (Body-SRT) of lung and liver tumors., Methods and Materials: Representative patient cases of lung and liver tumors were chosen for analysis. A PTV was constructed for each case and plans were generated which employed an array of block margins ranging from -2.5 mm to 10 mm at isocenter. Plans were generated for cerrobend blocks and for a multileaf collimator. The prescription isodose coverage was renormalized for each case and dose-volume histograms (DVH) and normal tissue complication probabilities (NTCP) were determined for each plan., Results and Conclusion: For the cases studied, the optimal block margin was in the 0.0 mm range. The ranking of plans was identical for both dose-volume based and biological based criteria. The method of blocking had no significant effect on treatment plans. The use of narrow margins for Body-SRT results in normal tissue sparing and creates significant target dose inhomogeneity which may be beneficial for tumor control.

Purpose: Brachytherapy has long been used to deliver localized radiation to the breast and other cancer sites. For interstitial implants, proper source positioning is critical in obtaining satisfactory dose distributions. The present work examines techniques for optimizing source guide placement in high-dose-rate (HDR) biplanar implants, and examines the effects of suboptimal catheter placement., Methods and Materials: Control of individual dwell times in HDR implants allows a high degree of dose uniformity in planes parallel to the implant planes. Biplanar HDR implants can be considered optimized when the dose at the implant center is equal to the dose at the symmetric target boundaries. It is shown that this optimal dose uniformity is achieved when the interplanar separation is related to the target thickness T through the direct proportionality, s = T/square root2. To quantify the significance of source positioning, the average dose and a related quantity, equivalent uniform dose (EUD), were calculated inside the treatment volume for two conditions of suboptimal catheter geometry. In one case, the interplanar spacing was varied from 1 cm up to the target thickness T, while a second study examined the effects of off-center placement of the implant planes., Results: Both the average dose and EUD were minimized when the interplanar spacing satisfied the relationship s = T/square root2. EUD, however, was significantly smaller than the average dose, indicating a reduced relative cell killing in the high dose regions near the dwell points. It was also noted that in contrast to the average dose, the EUD is a relatively weak function of catheter misplacement, suggesting that the biological consequences of suboptimal implant geometry may be less significant than is indicated by the increase in average dose., Conclusion: A concise formula can be used to determine the interplanar separation needed for optimal dose uniformity in Manchester-type implants. Deviations from optimal source geometry result in an increase in the average dose inside the treatment volume, but the weaker dependence of the EUD suggests that the surviving fraction of cells may not be not strongly affected by suboptimal source geometry.

Ionizing radiation at 2 Gy activates the epidermal growth factor receptor (EGFR) kinase activity in A431 squamous carcinoma cells and as a consequence transiently activates a downstream effector, mitogen-activated protein kinase (MAPK). A dose-response analysis shows fourfold activation 3-5 min after irradiation at 0.5 Gy with no additional activation after doses up to 4 Gy. Activation is independent of protein kinase C as defined by marginal effects of protein kinase C down-regulation and the protein kinase C inhibitor, chelerythrine. In contrast, an intracellular Ca2+ chelator (BAPTA/AM), a Ca2+ antagonist (TMB-8) and a phospholipase C inhibitor (U73223), which inhibits radiation-induced Ca2+ oscillations, all block MAPK stimulation. The upstream component, Raf-1, is also activated through a mechanism that is dependent on EGFR and Ca2+. Activation of Raf-1, monitored by tyrosine phosphorylation and co-immunoprecipitation with Ras, was inhibited by BAPTA/AM and TMB-8, indicating that the Ca2+-dependent step occurs at or before the interaction of Ras and Raf-1. Neither the Ras guanosine triphosphate exchange protein, SOS, nor Ca2+-activated tyrosine kinases linked to the MAPK pathway, focal adhesion kinase and PYK2, were stimulated by radiation. In contrast, EGF activated SOS as shown by the enhanced association of SOS with EGFR in co-immunoprecipitation experiments. These results suggest that activation of EGFR-dependent downstream signaling induced by radiation differs from that induced by the natural ligands of EGFR.

Ionizing radiation is believed to stimulate the repopulation of squamous carcinoma cells that survive the early portion of a fractionated course of radiotherapy. To characterize any intrinsic radiation-induced adaptive response and to examine whether epidermal growth factor (EGF) influences this response, A431 and 183A cells were irradiated with repeated daily exposures of 0.5-0.75 Gy and then grown in monolayer culture for 7 days with or without EGF at a 1 ng/ml concentration. Cell numbers were quantified using a microtiter dye-reduction assay. EGF alone caused approximately 70% and 30% growth inhibition of human SC A431 and 183A cells, respectively. Although radiation alone did not affect proliferative rates in these conditions, radiation eliminated the EGF-related growth inhibition in both cell lines. This effect was dose dependent in single radiation exposure experiments. Cell cycle analyses indicated that EGF initially promoted entry into S-phase 3 days after treatment but caused a G1-S block after 7 days. Treatment with radiation recruited cells into S-phase and G2-M, an effect which was sustained 7 days after treatment, overriding the influence of EGF. Radiation-induced modulation of the response of human squamous carcinoma cells to EGF in vitro after single and repeated radiation exposures suggests a proliferation response that may underlie enhanced repopulation of tumor clonogens in vivo.

Flunarizine is a class IV calcium channel blocker which increases oxygen delivery to hypoxic regions in solid tumours, exerting a radiosensitising effect in vivo in animal tumour models. Precisely how the drug improves oxygenation is not well understood. We hypothesised that metabolic conditions present within solid tumours reduce red blood cell (RBC) deformability and that flunarizine exerts its in vivo effect by preventing this loss of RBC deformability. A microrheometer was used to compare the viscosity of rat and human RBC suspensions in conditions of hypoxia (pO2 < 10 mmHg), acidic environment (pH 6.8), and elevated lactate concentration (lactate 5 mMol l-1), without or with flunarizine at concentrations of 5, 10, and 50 mg l-1. The effects of flunarizine on RBC density and morphology were also recorded. Hypoxia, low pH, and lactate exposure together increased both human and rat RBC suspension viscosity. Flunarizine at concentrations of 5 and 10 mg l-1 prevented the increases in viscosity. The drug caused dose-dependent shifts toward lower cell density while inducing a characteristic cupped shape (stomatcytic morphology), suggesting a mechanism involving calmodulin inhibition. The results support the hypothesis that flunarizine improves tumour blood flow and oxygenation by enhancing flow properties of RBC's in solid tumours.